Joint association of hyperuricemia and reduced GFR on cardiovascular morbidity: a historical cohort study based on laboratory and claims data from a national insurance provider

Abstract

Background: Hyperuricemia is common in patients with chronic kidney disease (CKD). We assessed the relationship of increased serum uric acid levels with cardiovascular risk across levels of kidney function.

Study design: Historical cohort study.

Setting & participants: Study data were drawn from administrative records of a national private health insurer (2003-2006). We included all adult beneficiaries with concurrently measured serum creatinine and serum uric acid. Patients with acute kidney failure or undergoing renal replacement therapy at baseline were excluded.

Predictors: Serum uric acid concentration and estimated glomerular filtration rate (eGFR).

Outcomes & measurements: Cardiovascular diagnoses (myocardial infarction, subacute coronary heart disease, heart failure, cerebrovascular disease, or peripheral arterial disease) ascertained from billing claims. Cox proportional hazard models were used to test the association of predictors with cardiovascular morbidity. Models were adjusted for sociodemographic characteristics, selected comorbid conditions, and laboratory results.

Results: In 148,217 eligible patients, mean eGFR was 84 mL/min/1.73 m(2) and the prevalence of CKD stages 3-5 was 6.0%. Hyperuricemia (serum uric acid >7 mg/dL) was found in 15.6% of patients. The 40-month cumulative incidence of cardiovascular events (mean follow-up, 15.3 months) was 8.1%. Cardiovascular risk was associated independently with uric acid level, and this association was stronger in patients with lower eGFRs.

Limitations: Observational design, lack of information for mortality and potential confounders, single creatinine and uric acid assessment.

Conclusions: Serum uric acid concentration was an independent correlate of cardiovascular morbidity, and this association was stronger in patients with severely decreased eGFR. This investigation provides a rationale for further study of serum uric acid-lowering interventions on cardiovascular risk in the general population and patients with CKD.